CCD and MHS are allelic conditions both due to (predominantly dominant) mutations in the skeletal muscle ryanodine receptor (RYR1) gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1).
CCD has recently been linked to two novel deletions (c.12640_12648delCGCCAGTTC [p.Arg4214_Phe4216del] and c.14779_14784delGTCATC [p.Val4927_Ile4928del]) in the C-terminal region of RYR1.
CCD mutations in RyR1 have been proposed to lead to the formation of sarcoplasmic reticulum (SR) Ca(2+) release channels that are excessively leaky to Ca(2+).
CCD is thought to arise from Ca(2+)-induced damage stemming from mutant RyR1 proteins forming "leaky" sarcoplasmic reticulum (SR) Ca(2+) release channels.
CCD has been linked to the gene encoding the ryanodine receptor (RYR1) and is considered to be an allelic disease of malignant hyperthermia susceptibility.